PROJECT ABSTRACT Prcis: Our goal is to conduct secondary data analyses on a comprehensive data set from a randomized controlled trial (RCT) designed to determine the energy balance mechanisms underlying the differential early weight gain experienced by infants who were fed isocaloric infant formulas that differed in the form of protein. In addition to accomplishing the primary aims, we collected multiple and diverse phenotypes from mother- infant dyads during the RCT, which lasted from 2 weeks postpartum until infants were 12.5 months, with a follow-up evaluation at 1.5 years. Therefore, we have a unique opportunity that go beyond the goals of the original RCT to assess direct and indirect effects of early diet on the highly pervasive phenomenon of nutritional programming. The trial randomized a diverse group of healthy infants (60% black Americans) to feed either cow milk formula (CMF) or an isocaloric extensively hydrolyzed formula (EHF) for the first year of life. Randomization to CMF, compared to EHF, significantly increased the likelihood of early rapid weight gain, a risk factor for later obesity, via differences in energy in and out. Additional phenotypes (secondary outcomes) collected throughout the RCT included measures of developmental milestones, diet, maternal feeding styles, food preferences, and taste genotype. These data will be subjected to secondary analyses and, depending on the hypothesis, compared with primary outcomes of anthropometry, early weight gain, adiposity, and physical activity. At the heart of the proposal are five aims, which upon completion will yield at least six publications. AIM 1 will test how proposed risk factors (early rapid weight gain, low physical activity, delayed motor development) and biomarkers (timing of primary teeth eruption), independently or in combination, predict adiposity and Z scores at 12.5 months and 1.5 years. AIM 2 will determine from monthly diet records the formula-feeding patterns and from questionnaires the feeding practices of mothers, to test the hypothesis that type of formula in the bottle is a bigger contributor to early weight gain trajectories and childhood obesity than are maternal feeding practices. Because EHF tastes more bitter than CMF, AIM 3 will test the hypothesis that EHF-fed infants will be more accepting than CMF-fed infants of broccoli-flavored food; genetic variation in a known bitter taste receptor activated by glucosinolates in broccoli will be factored in the analyses. AIM 4 will characterize the pattern, quality, and nutrient content of the diet of mothers over time and concordance with their children?s diets. AIM 5 will provide descriptive data related to (a) contribution of energy from formula versus non-formula each month during the first year of life and (b) determination of the accuracy of empiric equations used to estimate infant basal metabolic and total energy expenditure, by comparisons with actual measures of energy expenditure. These analyses will add to the knowledge base on early programming, with the goal of improving the health of the next generation of infants who are formula fed.